The role of virus neutralisation in immunity to feline immunodeficiency virus infection

QR180 Immunology;QR Microbiology;RB Pathology;QR355 Virology

Samman, Ayman ; Hosie, Margaret

University:University of Glasgow

Department:School of Veterinary Medicine

关键词: Feline Immunodeficiency Virus, FIV, neutralising antibodies, NAbs, virus neutralisation assay, VNA, N-linked glycosylation, PNGS, mutagenesis, luciferase, enhancement, aNAbs, bNAbs, HIV, phylogeny, UK, subtype A, neutralisation determinant, V3, C3-V4, V5, V1/V2 analogue, cat, Env, vaccine;   

Others  :  http://theses.gla.ac.uk/1554/2/Samman.pdf

来源: University of Glasgow

【 摘 要 】

Feline immunodeficiency virus (FIV) is an important veterinary pathogen with comparative significance because of its similarities to its human counterpart HIV.Since FIV is the only non-primate lentivirus which induces AIDS-like symptoms in its natural host, it serves as a valuable animal model for both prophylactic and therapeutic studies of HIV.It is accepted that the induction of neutralising antibodies (NAbs) is a key element in the control of lentiviral infection, since T-cell based vaccines alone failed to prevent infection in most experimental animal model systems. In this project a robust and reproducible in vitro neutralisation assay was developed and optimised, permitting the assessment of the NAb response in naturally infected cats and with the potential to evaluate candidate vaccines.It was demonstrated that, in general, primary FIV strains in the UK belong to subtype A, and therefore the development of a regional, subtype A-specific, FIV vaccine could be considered for use in the UK.The identification of a neutralisation resistant isolate of FIV led to the finding that a linear neutralisation determinant was located within the V5 region of Env and mutations in this region may lead to immune evasion in vivo.In addition, a second neutralisation determinant was identified in the C3/V4 region of Env.Finally, it was observed that a small proportion of naturally infected cats generated NAbs against FIV.Of these, only a very small proportion of the cats had antibodies with the potential to cross neutralise strains within the same subtype as the homologous isolate.Nonetheless, a plasma sample from a single cat was identified that neutralised all strains tested, including strains from different subtypes and geographical regions.It is likely that studies of the homologous isolate that induced the broad NAb response may be capable of inducing a similar broad response in vaccinated cats.Such a finding would have important implications for the design of potential novel lentiviral immunogens.